the movement of gas between the environment & the blood
1. transport between the atmosphere & the alveolus (breathing)
2. diffusion across the alveolar/capillary membranes into the blood
Fick’s Law of Diffusion
states that the volume of a gas that passes through a barrier is a function of the area of the barrier divided by its thickness * the diffusion constant * the partial pressure gradient for the gas across the membrane (ΔP)
Vgas ∝ A/T * D * (P1–P2)
the gasses we’re interested = O2 & CO2
Diffusion Coefficient (Constant)
is a function of the solubility of the gas in question divided by the square root of its molecular weight
D ∝ Sol / √MW
units = mL/min * mmHg
it’s directly proportional to the solubility of a gas & inversely proportional to the square of its molecular weight
a gas will dissolve in a liquid in proportion to its partial pressure over the liquid
the actual amount that dissolves = the solubility coefficient * partial pressure
Which is more soluble in aqueous solution, CO2 or O2?
CO2 is ~ 20x more soluble than O2
therefore it diffuses more rapidly EVEN THOUGH it has a higher MW (CO2 = 28 Da, O2 = 16 Da)
Solubility of O2 & CO2 in Plasma
[O2]diss = 0.003 mL O2 / dL / mmHg * PO2
[O2]diss = 0.06 mL CO2 / dL / mmHg * PO2
0.003 mL of O2 will dissolve in a deciliter of aqueous solution per mmHg
would multiply that times the partial pressure of oxygen in the blood if you want to find out HOW MUCH O2 is dissolved in the blood
At what rates do CO2 & O2 diffuse across alveolar/capillary membrane?
both gasses diffuse at similar rates
although CO2 is more soluble, the driving force for diffusion (ΔP) is GREATER for O2 than CO2
the partial pressure difference for O2 across the alveolar/capillary barrier is ~60 mmHg
for CO2 it’s only 6 mmHg
What is capillary transit time for RBCs in the pulmonary system?
0.75 seconds - gas exchange occurs VERY quickly
equilibration of O2 & CO2 occurs in ~ 0.3 sec so there is ample time for gas equilibration to occur
What factors can alter transit time?
exercise REDUCES the transit time
however there is still adequate reserve to fully exchange the gases
What happens to gas exchange at high altitudes?
at high altitudes there’s a lower PatmO2
this reduces the alveolar-capillary partial pressure gradient for oxygen, meaning there might not be
enough DRIVING FORCE to fully load the blood w/ O2 during normal transit time
How would you measure the diffusion capacity of the lung?
using Carbon Monoxide (CO)
a subject breathes a low CO-air mixture
PACO is high
CO would normally bind STRONGLY to hemoglobin
however b/c capillary (RBC) PCO fails to reach alveolar PCO, the uptake of CO must be diffusion limited
How would you measure the perfusion limitations of gas exchange?
using Nitrous Oxide (N2O)
N2O doesn’t combine w/ hemoglobin, therefore as N2O exchanges across the alveolar-capillary barrier, the PN2O rises rapidly & reaches that of the alveolar gas (PAN2O) only 1/10 of the way along the capillary
the amount of N2O taken up by the blood depends upon the blood flow (how fast it passes through the capillaries) & not on the diffusion properties of the barrier – it is perfusion LIMITED
What does it mean to be perfusion limited?
it means that the amount of gas that can be transferred into the blood is dependent on HOW MUCH blood passes through the capillaries
more blood → more gas (high Pgas)
*oxygen is perfusion limited: get more oxygen in blood by having a higher perfusion rate
What is true about both O2 & CO2?
they both reach equilibrium between blood & alveolar partial pressures
they are perfusion LIMITED in a healthy individual
What happens to the equilibrium between blood & alveolar partial pressures in pulmonary diseases that increase the thickness of alveolar-capillary walls?
the diffusion coefficient DECREASES - O2 might defuse more slowly
the PO2 at the end of the capillary may be BELOW the PAO2 (equilibrium isn’t reached)
less O2 makes it into the blood*
eg. COPD (destroys pulmonary capillaries), diffuse fibrosis of pulmonary parenchyma, or loss of functional tissue from a tumor or surgery
What equation can be used to calculate alveolar oxygen (PO2)?
the Alveolar Gas Equation
PAO2 = PIO2 – (PaCO2 / 0.8)
PAO2: alveolar oxygen
PIO2: partial pressure of O2 in inspired (tracheal) air (~160 mmHg)
PaCO2: the arterial PCO2
0.8: the respiratory exchange ratio (volume of CO2 expired per volume of O2 inspired)
PAO2 = 143 – (40 / 0.8) = 103 mmHg
alveolar arterial difference in O2
in healthy individuals this is ~4 mmHg
is the difference between alveolar gas & mixed arterial blood even after complete equilibration
normal alveolar PO2 ~ 104 mmHg, but arterial PO2 is ~ 100 mmHg
What causes A-aDO2?
an imperfect balance between ventilation & perfusion of the lung - bronchial circulation especially
What happens to A-aDO2 in normal subjects with age (over time)?
it INCREASES w/ both age & loss of lung compliance
over 30, the A-aDO2 = age * 0.3 mmHg
What would an abnormally high A-aDO2 indicate?
a pathological problem in which gas exchange is compromised
eg. emphysema, pneumonia, asthma, etc.
usually indicates a difficulty of getting O2 from the alveoli into the blood stream
Low O2 Solubility Causes a Problem
we want to carry O2 from the lungs → tissue
w/ an arterial PO2 of 104 mmHg, dissolved O2 is low (0.003 * 104 = 0.312 mL/dL) ~ 1.5% of the total content
0.312 mL/dL is the maximum amount of oxygen we can dissolve in water at alveolar pressure
What is an adaptation that increases oxygen-carrying capacity, seeing as how plasma (aq. soln) can only carry 0.312 mL/dL?
Hemoglobin (Hb) carries the remaining O2
Hb has 4 polypeptide chains, each containing a heme group (porphyrin ring w/ a ferrous ion)
each heme group binds one O2 molecule
therefore Hb can sequentially bind up to 4 O2
What does adding Hb to a solution do in terms of amount of O2 able to diffuse into that solution?
adding Hb (to side B) lowers PO2 as oxygen binds to the Hb (it becomes part of the protein - no longer contributes to the PO2 which is only made up of diffused O2)
free, dissolved oxygen from the other side (A) now diffuses into side B, down its gradient
total oxygen is the same in the solutions but the PO2 is much lower → the overall oxygen content on side B is GREATER than on side A